ABSTRACT
The clinical phenotypes and genotypes of a child with autism spectrum disorder (ASD) concomitant with MYT1L gene mutation were analyzed retrospectively, who was admitted to the Department of Rehabilitation Medicine of Henan Children′s Hospital in April 2019.Whole genome sequencing and copy number variations detection were performed on the child and relevant articles about MYT1L mutation were subjected to a literature review.It was found that this child had a missense mutation of MYT1L gene (c.2186T>G, p.Met729Arg) in 15 exon and was in a state of chimera, with about 10% of the mutation rate.This mutation was not identified in the parents and brother of this patient.A total of 18 reports of MYT1L-related genetic abnormalities were retrieved, including 53 patients in total (including this case), including 22 patients with point mutations and 30 patients containing MYT1L gene region with 2p25.3 chromosomal microdeletions.The incidence of autism was 45.0% (18/40 cases), that of overweight/obesity was 70.2% (33/47 cases) and that of dysnoesia/hypoevolutism was 96.2%(51/53 cases). However, chimeras had relatively mild symptoms.It indicates that the mutation of MYT1L is an important risk factor of ASD, but chimeras have mild symptoms.The children with ASD who are obese or overweight should be alerted to the possible presence of MYT1L mutation, and genetic testing can be performed to confirm the diagnosis and the possibility of chimerism.The spectrum of genetic mutations in ASD was expanded in this study.
ABSTRACT
The differentiation and maturation of oligodendrocyte precursor cells (OPCs) is essential for myelination and remyelination in the CNS. The failure of OPCs to achieve terminal differentiation in demyelinating lesions often results in unsuccessful remyelination in a variety of human demyelinating diseases. However, the molecular mechanisms controlling OPC differentiation under pathological conditions remain largely unknown. Myt1L (myelin transcription factor 1-like), mainly expressed in neurons, has been associated with intellectual disability, schizophrenia, and depression. In the present study, we found that Myt1L was expressed in oligodendrocyte lineage cells during myelination and remyelination. The expression level of Myt1L in neuron/glia antigen 2-positive (NG2) OPCs was significantly higher than that in mature CC1 oligodendrocytes. In primary cultured OPCs, overexpression of Myt1L promoted, while knockdown inhibited OPC differentiation. Moreover, Myt1L was potently involved in promoting remyelination after lysolecithin-induced demyelination in vivo. ChIP assays showed that Myt1L bound to the promoter of Olig1 and transcriptionally regulated Olig1 expression. Taken together, our findings demonstrate that Myt1L is an essential regulator of OPC differentiation, thereby supporting Myt1L as a potential therapeutic target for demyelinating diseases.